These experiments are based on the hypothesis that patients with sickle cell disease (SCD) have chronic deficiency of the amino acid arginine, and that this deficiency plays a major role in the pathogenesis of some of the acute ischemic and chronic end-organ complications of this disease. If this hypothesis is true, then long-term arginine (ARG) supplementation may be beneficial to these patients. Since the liver displays a high level of arginase activity, the bioavialability of arginine may be limited; therefore, supplementation with citrulline may be a preferable method of increasing plasma arginine concentrations. The research has 2 specific aims: Aim 1. To obtain preliminary data regarding the baseline status of arginine metabolites in patients with SCD. Aim 2. To determine the metabolic and hemodynamic effects of short-term (1 week) oral citrulline 9CIT) and ARG supplementation in these patients. The goal is to recruit sixteen subjects with sickle cell anemia (HbSS) and 16 normotensive black controls between the ages of 14 and 45 with normal serum creatinine. To date, seven subjects with sickle cell disease and 1 control have been enrolled. Patients are fed a daily diet controlled containing 6 grams arginine, 4 grams sodium, low nitrate and nitrite diet for one week at a time. They are studied three conditions: baseline diet, baseline diet plus oral citrulline (1200 mg po tid and at bedtime) and baseline diet plus oral arginine (1400 mg po tid and at bedtime). For the first 4 days of each study week, they collect the food as an outpatient, and for the last 3 days, they are hospitalized in the GCRC during which time they undergo blood and urine collections for determination of amino acids, nitrate and nitrite (i.e. the stable metabolites of nitric oxide), urea, creatinine, sodium and cGMP (urine only). Blood pressure is monitored as well.